On July 5, 2023 Intensity Therapeutics, Inc. ("Intensity" or the "Company") (Nasdaq: INTS), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported the closing of its upsized initial public offering of 3,900,000 shares of common stock at a public offering price of $5.00 per share (Press release, Intensity Therapeutics, JUL 5, 2023, View Source [SID1234633067]). In addition, Intensity has granted the underwriters a 45-day option to purchase an additional 585,000 shares of its common stock at the initial public offering price, less the underwriting discounts and commissions.

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In connection with the offering, the Company’s common stock began trading on The Nasdaq Capital Market on June 30, 2023, under the ticker symbol "INTS."

The net proceeds to Intensity from the offering (prior to any exercise of the underwriter’s over-allotment option), after deducting the underwriting discounts, commissions and transaction expenses were approximately $16.2 million.

The Benchmark Company and Freedom Capital Markets acted as the joint book-running managers for the offering.

The securities described above were being offered by the Company pursuant to a registration statement on Form S-1 (Registration No. 333-260565) that was previously filed with the U.S. Securities and Exchange (the "SEC") and declared effective on June 29, 2023. This offering was made only by means of a prospectus forming part of the effective registration statement. Copies of the final prospectus can be obtained through the SEC’s website at www.sec.gov or from: The Benchmark Company, LLC, Attention: Prospectus Department, 150 E. 58th Street, 17th floor, New York, NY 10155 at 212-312-6700 or by email at [email protected] and Freedom Capital Markets, 40 Wall Street, 58th Floor, New York, NY 10005, via email at [email protected] and via telephone at (800) 786-1469.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful.

On July 5, 2023 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of pioneering immunotherapies, reported the publication of a manuscript entitled "CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation" in the latest issue of The Journal for Immuno-Therapy of Cancer (JITC) (Press release, I-Mab Biopharma, JUL 5, 2023, View Source [SID1234633066]).

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Givastomig is engineered to bind to CLDN18.2-expressing cancer cells and co-stimulatory receptor 4-1BB on adjacent T cells, with the aim of activating T cells specifically within CLDN18.2-expressing tumors and triggering a potent tumor-killing effect. This innovative approach offers the potential for effective and targeted immuno-therapy in gastric cancer, a disease characterized by a poor prognosis and limited treatment options.

Results from this study demonstrated that 4-1BB+ T cells co-exist in close proximity to CLDN18.2+ gastric cancer cells in patients. Moreover, givastomig bound to tumor cells across a wide range of CLDN18.2 expression levels and induced 4-1BB activation only in the context of CLDN18.2 binding, indicating the targeted effect of 4-1BB activation in the presence of CLDN18.2+ cells. In the in vivo CLDN18.2-expressing tumor model, givastomig induces localized immune activation in tumors, increasing the ratio of CD8+/Treg cells, resulting in superior anti-tumor activity and long-lasting memory response against tumor rechallenge.

"The findings from our research demonstrate the significant potential of givastomig in treating gastric cancer patients with varying levels of CLDN18.2 expression," said Dr. Lin Shen, Professor of Clinical Oncology at the Beijing Cancer Hospital of Peking University, and Director of SIP LifeLink Oncology Research Institute. "By activating 4-1BB signaling in a CLDN18.2 engagement-dependent manner, givastomig can avoid the risk of liver toxicity and systemic immune response commonly observed with other 4-1BB stimulating agents in previous clinical trials."

"We are excited to see this manuscript published in JITC, as it showcases the innovative design and remarkable anti-tumor activity in preclinical models of givastomig," said Dr. Andrew Zhu, President of I-Mab. "This molecule has demonstrated promising results in this study by effectively activating T cells and triggering a localized immune response within the tumor microenvironment. With ongoing clinical studies, we aim to build upon these findings and ultimately make this innovative therapy accessible to patients with gastric cancer."

Givastomig is currently undergoing Phase 1 clinical studies both in the U.S. and in China. Encouragingly, the Phase 1 study has shown favorable safety profile and promising efficacy signals thus far. The Company intends to report additional clinical data from the study at a major medical conference in the second half of the year.

About Givastomig

Givastomig, also known as TJ-CD4B/ABL111, is a Claudin 18.2 and 4-1BB bispecific antibody capable of binding to tumor cells expressing Claudin 18.2, i.e., gastric cancer and pancreatic cancer cells, and stimulating intra-tumoral T cells by the 4-1BB arm designed to be activated only upon tumor engagement while silent elsewhere. Givastomig effectively maintains a strong tumor binding property and anti-tumor activity attributable to a synergistic effect of both Claudin 18.2 antibody and 4-1BB antibody while avoiding or minimizing liver toxicity and systemic immunotoxicity commonly seen with 4-1BB antibodies as a drug class. Being developed under collaboration between I-Mab and ABL Bio, a clinical-stage biotechnology company in South Korea, givastomig is currently being investigated in a phase 1 clinical study in the U.S. and China. In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for givastomig for the treatment of gastric cancer, including cancer of gastroesophageal junction.

On July 5, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported the publication of preclinical data demonstrating that a strategy based on the company’s proprietary Chimeric Antigen Receptor-Cytokine Induced Killer (CAR-CIK) cell platform provides advantages over single-targeting CARs including improved efficacy and high specificity in a model of acute myeloid leukemia (AML) (Press release, CoImmune, JUL 5, 2023, View Source [SID1234633065]). The preclinical data are published in Blood Advances, a peer-reviewed journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

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"CAR-engineered T-cells have demonstrated high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML," said Andrea Biondi, M.D., Professor of Pediatrics at the University of Milano-Bicocca and Scientific Director of the M. Tettamanti Research Center. "The impressive safety profile and encouraging activity of CAR-CIK cells is particularly attractive in the AML setting, in which older age and comorbidities hamper adoptive cell therapy options because of the risk of severe cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome."

The publication, titled, "IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML," describes an approach to developing CAR-CIK cells that co-express a first-generation low affinity anti-CD123 interleukin-3–zetakine (IL-3z) and an anti-CD33 as co-stimulatory receptor without activation signaling domains (CD33.CCR). The dual strategy demonstrated powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells (HSPCs) and endothelial cells. Specifically, the researchers found:

CD123 and/or CD33 knockout impairs leukemia growth by modulating multiple cancer pathways in a model of NPM1-mutated AML.
CAR-CIK cells mediate high antileukemic efficacy through transacting co-stimulation.
Low affinity CAR-CIK cells decrease on-target/off tumor toxicity against endothelial and HSPCs in vitro.
Low affinity CAR-CIK cells preserve antileukemic efficacy in vitro and improve antitumor control in vivo.
"CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen," said Sarah Tettamanti, Ph.D., Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. "In this study, we describe a novel strategy using CAR-CIK cells to target both CD33 and CD123 without the risk of severe on target/off-tumor toxicities. This approach has the potential to improve the outcome of patients with AML."

On July 5, 2023 10x Genomics, Inc. (Nasdaq: TXG), a leader in single cell and spatial biology, reported that its single-cell genomic technologies were used in a study published in the journal Nature Medicine about new gene signatures that explain why some children with leukemia have longer remission after CAR T-cell therapy (Press release, 10x Genomics, JUL 5, 2023, View Source [SID1234633064]). The collaborative research project was conducted by researchers from Great Ormond Street Hospital (GOSH), the Wellcome Sanger Institute and the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH).

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Researchers conducting the study, "Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia," used Chromium Single Cell Gene Expression technologies and T-cell receptor sequencing of samples to look at what makes the long-lasting CAR T-cells unique. These helped identify a genetic signature of the CAR T-cells that persisted in the body long-term – an important predictor of durable remission. The data was from the CARPALL trial, which used molecular features and clonal dynamics of CD19 CAR T-cells of 10 children with relapsed or refractory B-cell acute lymphoblastic.

Ben Hindson, Co-founder and Chief Scientific Officer at 10x Genomics, said, "Single cell genomics is a powerful tool that is transforming cancer research and our understanding of health and disease. We are so proud to have 10x technologies behind this incredible breakthrough. We celebrate the achievements of the research team and the selfless dedication of the families who made this study possible. We look forward to continuing to give researchers the technologies needed to fuel new biological discoveries and ultimately help improve patient care."

Using Chromium Single Cell Gene Expression products, researchers identified a unique double negative phenotype of long-lasting CAR T-cells, which provides insights into how these cells survive and remain active in the body. These key genes appeared to enable the CAR T-cells to persist and therefore allow the children to live cancer free long-term. The findings may lead to discovering new biomarkers that could predict the long-term durability of CAR T-cell therapies and provide better treatment options for patients.

Dr. Sam Behjati, co-senior author, Group Lead and Wellcome Senior Research Fellow at the Wellcome Sanger Institute and Honorary Consultant Paediatric Oncologist at Addenbrooke’s Hospital, Cambridge, said, "This study is a fantastic step forward in our understanding of CAR T-cell persistence and illustrates the power of collaborative science and combining pioneering clinical research with cutting-edge genomic science. It is crucial that we continue to develop and build on these new treatments to help more children with leukaemia across the world."

On July 5, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has approved a registrational pivotal Phase III study of olverembatinib, Ascentage Pharma’s lead drug candidate, in combination with chemotherapy (investigational arm) comparing imatinib in combination with chemotherapy (control arm) for treatment of patients with naïve Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) (Press release, Ascentage Pharma, JUL 5, 2023, View Source [SID1234633063]). This approval marks a major milestone that could potentially pave the way for olverembatinib to become the first China-approved tyrosine kinase inhibitor (TKI) for the treatment of patients with Ph+ ALL in the first-line setting.

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Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival (PFS), and poor prognosis. Prior to the introduction of TKIs, a class of targeted small molecule compounds, allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving complete responses (CRs) from chemotherapy was widely adopted as a first-line treatment for patients with Ph+ ALL. However, the five-year overall survival (OS) was only less than 30% and more than 70% patients relapsed before the transplantation or simply lacked access to the surgical treatment[1]. The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL, although first and second-generation TKIs have considerable limitations, including high relapse rates and disappointing long-term survival with a three to five-year OS rate of just about 50%[2]. These limitations are primarily caused by low complete molecular responses (CMRs) and T315I kinase domain mutations, thus leaving substantial room for improvement in the treatment of Ph+ ALL. Currently, no TKI has been approved for the first-line treatment of Ph+ ALL in China and third-generation TKIs with more potent efficacy can potentially provide better prognosis for patients with Ph+ ALL by inducing a higher rate of CMRs and inhibiting the T315I mutation.

Ascentage Pharma’s novel drug candidate, olverembatinib, is an orally-administered third-generation TKI and the first and only China-approved third-generation BCR-ABL inhibitor. Currently, olverembatinib is being jointly commercialized by Ascentage Pharma and Innovent Biologics. Olverembatinib was approved by the CDE of the China NMPA in November 2021 for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. Previously, olverembatinib received a recommendation from the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment Hematologic Malignancies as a treatment option for patients with Ph+ ALL.

"This approval for the pivotal Phase III study in newly diagnosed patients with Ph+ ALL marks a major milestone for the development of olverembatinib," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "TKIs combined with chemotherapy is a widely recognized standard treatment strategy for patients with Ph+ ALL, but no TKI has been approved for the first-line setting in this therapeutic area, thus potentially making olverembatinib the first TKI approved for the first-line treatment of Ph+ ALL in China. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will expeditiously advance the clinical development of olverembatinib in efforts to allow more patients to benefit from this novel therapeutic as soon as possible."

References

1. Fielding A K, Rowe JM, Richards SM, et a1. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemo therapy in the pre imatinib era results from the International ALL Trim MRCUKALIXII/ECOG 2993. Blood, 2009,113: 4489- 4496.
2. Elias Jabbour et. Treatment of Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia-From Intensive Chemotherapy Combinations to Chemotherapy-Free Regimens: A Review. JAMA Oncol. 2022 Sep 1;8(9):1340-1348.

About Olverembatinib (HQP1351)

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the orally active, third-generation TKI olverembatinib is the first and only China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation.

In November 2021, olverembatinib was granted a conditional approval through the Priority Review process by the China National Medical Products Administration (NMPA) for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. Subsequently, Olverembatinib was included into the China 2022 National Reimbursement Drug List (NRDL) for the approved indication. In March 2021, olverembatinib was granted a Breakthrough Therapy Designation (BTD) by the CDE for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs. In July 2022, an NDA for this indication was accepted by the NMPA and subsequently granted a BTD that will support a full approval of olverembatinib.

In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. Since 2018, the clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meetings for five consecutive years, and was nominated for "Best of ASH (Free ASH Whitepaper)" in 2019. To date, olverembatinib has been granted one Fast Track Designation (FTD) and four Orphan Drug Designations (ODDs) from the US Food and Drug Administration (FDA) for the treatment of CML, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and gastrointestinal stromal tumour (GIST); and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.

In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.

*Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland.